Long-term follow-up and quality of life in patients with intracranial germinoma.

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group (p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients (p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival.

Change in treatment strategy for intracranial germinoma: long-term follow-up experience at a single institute.

BACKGROUND: Previous intracranial germinoma (IG) studies have investigated the effect of different radiotherapy (RT) volumes and the necessity for adjunctive chemotherapy, but there is currently no consensus on the best treatment for this tumor. METHODS: From January 1989 to December 2009, 80 IG patients (≤20 years old) were treated with various RT regimens. Of them, 14 patients had craniospinal irradiation (CSI) + primary boost (PB); 8 patients had whole-brain irradiation (WBI) + PB; 31 patients had whole ventricular irradiation (WVI) + PB; and 27 patients had focal RT only. Twenty-nine patients (36.2%) also received systemic chemotherapy (CHT). Survival was estimated by the Kaplan-Meier method and variables affecting survival were analyzed by the Cox proportional hazard model. RESULTS: Eleven patients (13.8%) developed local recurrence or dissemination after treatment, and 10 of these patients were in the focal RT group. The 5-year relapse-free survival (RFS) for the CSI, WBI, WVI, and focal RT patients were 100%, 85.7%, 100%, and 84.6%, respectively (P = .001). The 5-year overall survival (OS) for CSI, WBI, WVI, and focal RT patients was 100%, 83.3%, 100%, and 87.9%, respectively (P = .125). Focal irradiation (P = .02) and initial use of CHT (P = .021) were negatively associated with RFS. CONCLUSIONS: Focal RT plus CHT were associated with inferior control of IG and a higher incidence of CHT-related toxicities. Adjustment of the radiation volume to the whole ventricular system without CHT is sufficient for treatment of nondisseminated IGs, even with lower primary RT doses (<36 Gy).

Treatment strategies for initially disseminated intracranial germinomas: experiences at a single institute.

PURPOSE: Initially disseminated intracranial germinomas (IDIGs) can be observed in pre-adult and adolescent brain tumor patients. However, the disease prognosis is undetermined, and the method of optimal treatment remains controversial. METHODS: From January 1990 to January 2011, data on 91 intracranial germinoma patients (≤20 years old) were gathered from the Pediatric Brain Tumor database at Taipei Veterans General Hospital. A total of seven patients with a median age of 17.0 years had IDIGs (lesion sites >2), including IDIGs in the ventricular system or the spinal column. Craniospinal irradiation (CSI) plus a primary or metastatic boost was the mainstay strategy for radiotherapy. Six out of a total of seven patients (85.7%) also received systemic chemotherapy (CHT) after radiotherapy. Survivals rates between IDIGs and patients without dissemination were estimated using the Kaplan-Meier method. RESULTS: The median follow-up time for all seven patients was 67.5 months (range, 10.3-142.3 months). None of the IDIG patients experienced a recurrence or mortality after the completion of treatment. The 5- and 10-year disease-free survival (DFS) between IDIG and non-dissemination patients were 100%, 100%, 93.0% and 78.6%, respectively (p = 0.339). The 5- and 10-year overall survival (OS) between IDIGs and non-dissemination cases were 100%, 100%, 93.7% and 89.4%, respectively (p = 0.473). CONCLUSIONS: IDIG patients did not show reduced survival compared to non-dissemination patients if optimal radiotherapy and chemotherapy were used together.

Prognostic value of OCT4 in primary intracranial germinoma: a single institute analysis of 31 cases.

OCT4 expresses variably in primary intracranial germinomas. In this study, we tested our hypothesis that such variation of OCT4 is predictive of outcome in primary intracranial germinomas. Thirty-one histologically identified CNS germinoma patients were enrolled in our study. We collected medical data, immunohistochemically evaluated the OCT4 expression level, and followed up all patients from April 2001 to May 2010. We found that 7 of the 31 patients expressed OCT4 weakly, 11 expressed OCT4 moderately, and 13 expressed OCT4 strongly. No significant correlation between the OCT4 expression level and clinicopathological characteristics was observed. WV-CS combined treatment modality showed a better 5-year progression-free survival (PFS) rate than other treatment modalities and a low expression level of OCT4 showed a significantly better 5-year PFS. In both the WV-CS combined treatment modality and other treatments modality group, patients received a better 5-year PFS and had a lower level of OCT4 expression. As a result, we suggest OCT4 as a probable prognostic marker for intracranial germinoma.

[Prognostic factors analysis in patients with ovarian malignant germ cell tumor treated with fertility-preserving surgery].

OBJECTIVE: To analyse the clinicopathologic factors affecting prognosis and fertility of patients with malignant ovarian germ cell tumor (MOGCT). METHODS: The medical records and follow up data of 106 patients with MOGCT treated at Affiliated Tumor Hospital of Guangxi Medical University between January 1986 and December 2010.Kaplan-Meier method was used to analyse survival curves. The different prognoses between different clinicopathologic factor was evaluated by univariate analysis and log-rank test. The multivariate analysis was performed by the Cox proportional hazard regression method. Logistic regression analysis was used to evaluate the influence of different factors on the prognoses and fertility. RESULTS: The median age at primary treatment was 22 years old (range: 9 - 61 years old), 59 patients received fertility-preserving surgery, 45 patients received radical surgery, only 2 cases performed biopsy; 94 patients received postoperative adjuvant chemotherapy. Median follow-up time was 56.5 months (range: 2 - 309 months), there were 11 cases recurrences, 23 cases died from cancer. Of 47 patients live without tumor, 45 patients had normal menstrual. Of the 39 patients desiring pregnancy, 31 cases got 33 successful pregnancies, resulting in 33 live births. There is no statistically significant difference (P > 0.05) in progression free survival (PFS; 67.6% versus 63.3%) and overall survival (OS; 70.0% versus 64.1%) and mortality [15% (9/59) versus 31% (14/45)] between fertility-preserving surgery patients and radical surgery patients. The univariate analysis showed that the pathological types, postoperative residual tumor size, lymph nodes and omental resection were associated with OS (P < 0.1), and postoperative residual tumor size, chemotherapy cycles, lymph nodes and omental resection were associated with PFS (P < 0.1). The multivariate analysis showed only the postoperative residual tumor size was independent prognostic factor of OS (P = 0.039), and postoperative residual tumor size, chemotherapy cycles, lymph nodes resection were independent prognostic factors of PFS (P < 0.05). There is no statistically significant difference in OS, PFS and fertility between fertility-preserving surgery patients treated with or without a comprehensive staging surgery (P > 0.05). CONCLUSIONS: MOGCT can achieve a good prognosis after surgery combined chemotherapy. Postoperative residual tumor size is independent prognostic factor of PFS and OS. Comprehensive staging surgery could not improve prognosis. Fertility-preserving surgery plus adjuvant chemotherapy appeared to have little or no effect on prognosis and fertility.

Value of C-11 methionine PET/CT in patients with intracranial germinoma.

PURPOSE: The purpose of this study was to investigate the value of C-11 methionine (MET) positron emission tomography (PET)/computed tomography (CT) in patients with intracranial germinoma (IG). MATERIAL AND METHODS: We conducted a retrospective analysis of 21 consecutive patients with pathologically confirmed IGs and eight patients with intracranial non-germinomas (INGs) located in a similar region. Clinical characteristics, imaging findings, and tumor markers such as α-fetoprotein (AFP) and ß-human chorionic gonadotropin (HCG) were used as clinical variables. Maximum standardized uptake value (SUVmax), tumor-to-normal tissue (T/N) ratio, and visual scoring of tumor were used as MET PET parameters. RESULTS: All IGs were well visualized on MET PET with a three-grade visual scoring system. In addition, SUVmax of IGs was higher than that of INGs (P = 0.005). Pre-treatment (Pre-Tx) T/N ratio was significantly correlated with pre-Tx serum HCG (P = 0.031). Moreover, MET PET parameters showed significant associations with tumor location, sex, KRAS variant, and symptoms. CONCLUSION: MET PET/CT could be a useful diagnostic tool in patients suspected of having IGs. In addition, the MET avidity of tumor is a potential surrogate biomarker of HCG, which has been used as a diagnostic marker for IGs. Tumor MET parameters also had significant differences according to tumor locations, sex, symptoms, and KRAS mutation. However, MET avidity of tumors had no significant prognostic value.

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

PURPOSE: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities. MATERIALS AND METHODS: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months. RESULTS: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction. CONCLUSION: De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Update on current standard treatments in central nervous system germ cell tumors.

PURPOSE OF REVIEW: Various approaches have been used for the management of patients with germ cell tumors (GCTs) in the central nervous system (CNS); however, the optimal treatment of both germinoma and nongerminomatous GCTs remains unknown. This review discusses current management strategies and late effects of therapy for CNS GCTs. RECENT FINDINGS: To reduce the late complications of radiation therapy for patients with germinoma, many investigators have introduced dose reduction of radiation therapy in association with platinum-based chemotherapy. In addition, the radiation field has been restricted to the whole ventricular area for localized germinoma. This type of combination therapy has shown promising results and preserves cognitive function and quality of life. Despite various approaches including high-dose chemotherapy against highly malignant or relapsed GCTs, the prognoses of these patients remain dismal except for a few successful reports. SUMMARY: The 10-year survival rate of CNS germinoma is approximately 90%. Most patients with CNS GCTs are children and young adults. Therefore, with the improving life prognosis of young patients, secondary neoplasms, secondary cerebral vasculopathy, neurocognitive deficits, and many other adverse effects induced by the initial treatments are problems to be solved in the next decade.

[Retroperitoneal lymphadenectomy in disseminated non-seminoma germinogenic testicular tumors after chemotherapy in patients with elevated serum tumor markers].

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

Comparison between Craniospinal Irradiation and Limited-Field Radiation in Patients with Non-metastatic Bifocal Germinoma.

PURPOSE: Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature. MATERIALS AND METHODS: Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently. RESULTS: In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant. CONCLUSION: In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.

Primary intracranial germ cell tumors in children 36-year experience of a single center.

PURPOSE: Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%-3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT. PATIENTS AND METHODS: All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively. RESULTS: We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12-228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors. CONCLUSION: Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries.

Optimization of Intracranial Germinoma Treatment: Radiotherapy Alone with Reduced Volume and Dose.

PURPOSE: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx). METHODS AND MATERIALS: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis. RESULTS: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively. CONCLUSIONS: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable.

Intracranial Germ Cell Tumors in Adolescents and Young Adults: A 40-Year Multi-Institutional Review of Outcomes.

PURPOSE: The aim of this study was to determine the practice patterns and outcomes of intracranial germ cell tumors (IGCT) in adolescents and young adults according to different therapeutic approaches. METHODS AND MATERIALS: One-hundred twelve patients with IGCT aged 15 to 39 years were managed at either XX or the XY center from 1975 to 2015. The charts were retrospectively reviewed and data collected. RESULTS: Median duration of follow-up was 8.3 years. Ninety-four patients had germinomas, and 18 had nongerminomatous germ cell tumors (NGGCT). The primary disease sites were pineal gland (37 of 94 germinoma, 14 of 18 NGGCT) and suprasellar region (23 of 94 germinoma, 2 of 18 NGGCT). Eleven patients with germinoma (12%) and 2 patients with NGGCT (11%) had radiographic spinal metastases or positive lumbar cerebrospinal fluid cytology. Event-free survival (EFS) was 84% and overall survival (OS) was 90% at 10 years for germinoma; EFS was 71% and OS was 86% at 10 years for NGGCT. For patients with germinoma, 10-year EFS was 100% after craniospinal radiation therapy (CSRT) with chemotherapy (N = 10); 100% after whole-ventricular radiation therapy (WVRT), whole-brain radiation therapy (WBRT), or focal radiation therapy (FRT) with chemotherapy (N = 22); 90% after CSRT alone (N = 46); and 41% after WVRT, WBRT, or FRT alone (N = 16) (P < .0005). Ten-year OS was 100%, 100%, 90%, and 72%, respectively (P = .032). For patients with NGGCT, 10-year EFS was 80% after CSRT, WBRT, or WVRT plus chemotherapy (N = 10) versus 58% after FRT plus chemotherapy (N = 8) (P = .31); 10-year OS was 90% versus 58%, respectively (P = .16). CONCLUSIONS: We report excellent overall outcomes according to treatment approach in the largest study of IGCT in adolescents and young adults to our knowledge. EFS and OS were inferior after non-CSRT without chemotherapy in germinoma.

Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous hematopoietic stem cell rescue.

BACKGROUND: Adults and children with recurrent malignant central nervous system (CNS) tumors have a poor prognosis despite high dose chemotherapy with a conventional stem cell rescue regimen. In this study we evaluated the results of low dose, continuous infusion etoposide over 21 days added to a conventional high-dose regimen of carboplatin and thiotepa in eight patients with relapsed pediatric CNS tumors. PROCEDURE: Patients with high risk CNS tumors were treated with etoposide 25 mg/m(2)/day by continuous intravenous (IV) infusion from day -22 to day -2, carboplatin 667 mg/m(2)/dose IV (or area under the curve = 9 mg/ml/min according to the Calvert formula on days -8, -7, and -6, and thiotepa 300 mg/m(2)/dose IV on days -5, -4, and -3, followed by autologous hematopoietic stem cell rescue on day 0. RESULTS: Eight adults and children, with a mean age of 12.9 years (age range 5.6-27.8 years), with relapsed primary CNS tumors (metastatic medulloblastoma (7), germinoma (1)), were enrolled. The mean survival post-transplant was 4.8+ years, (range 8-160+ months). The 2- and 5-year overall survival rates were 75% and 50% respectively. None of the survivors required additional salvage irradiation. CONCLUSION: The strategy of low dose chronic exposure to a topoisomerase inhibitor along with ablative carboplatin and thiotepa with stem cell rescue showed promising survival outcomes in these relapsed patients. This treatment strategy deserves further evaluation in a larger group of high-risk or relapsed primary CNS tumors.

Treatment outcomes of intracranial germinoma: a retrospective analysis of 170 patients from a single institution.

PURPOSE: To perform a retrospective analysis of patients with intracranial germinoma treated in our department to evaluate treatment outcomes and determine optimal treatment strategies. METHODS: We reviewed the treatment outcomes of 170 patients with intracranial germinoma who were treated in our department from January 1996 to January 2017. The median patient age was 15 years old. Among the patients, 56 (33%) were pathologically diagnosed, and 114 (67%) were diagnosed clinically. Various radiation fields and doses were used. Cerebrospinal fluid (CSF) and serum beta-human chorionic gonadotropin (ß-HCG) levels were examined before treatment in 114 patients. Endocrinological evaluation was performed in 141 patients before and after treatment. A total of 38 patients received chemotherapy prior to radiotherapy (RT). The median follow-up time was 64.5 months (range 4-260.5 months). RESULTS: The 5- and 10-year overall survival (OS) rates were 94.5% and 91.3%, respectively. The relapse-free survival (RFS) rates at 5- and 10-years were 91.9% and 78.1%, respectively. Relapses occurred in 18 patients within 6 months-10 years. The spinal cord metastasis rate was 3.4% in patients with a localized lesion who did not receive spinal cord irradiation and 16.7% in patients with bifocal disease who were treated using whole ventricular irradiation (WVI) or whole brain radiotherapy (WBRT). Treatment failure did not occur in patients receiving chemoradiotherapy or in patients receiving three-dimensional conformal radiation therapy (3D-CRT)/intensity-modulated radiation therapy (IMRT). The RFS rate did not have a statistically significant correlation with the CSF/serum ß-HCG level. After RT, 19.1% of the patients developed newly impaired pituitary function and required hormone replacement therapy. CONCLUSIONS: WVI or WBRT+ primary boost (PB) is a sufficient irradiation field for localized intracranial germinoma, while patients with bifocal disease should undergo craniospinal irradiation (CSI), especially when treated with RT alone. CSF ß-HCG is not a prognostic marker for intracranial germinomas. The treatment results of chemotherapy followed by reduced-dose RT are comparable to those of RT alone. IMRT is recommended for intracranial germinoma to improve the target volume accuracy and decrease the complications of RT.

Upfront chemotherapy and involved-field radiotherapy results in more relapses than extended radiotherapy for intracranial germinomas: modification in radiotherapy volume might be needed.

PURPOSE: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma. METHODS AND MATERIALS: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months. RESULTS: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106). CONCLUSIONS: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.

Results of bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection for testicular cancer.

PURPOSE: We evaluated the feasibility and early oncological outcome of a laparoscopic nerve sparing bilateral retroperitoneal lymph node dissection. The surgical technique is described. MATERIALS AND METHODS: From July 2004 to December 2007 a total of 42 patients with nonseminomatous germ cell tumor (21 with stage I, 2 with stage IIA marker negative and 19 with post-chemotherapy stage IIB disease) underwent transperitoneal bilateral laparoscopic retroperitoneal lymph node dissection. The sympathetic trunk and postganglionic nerves were identified, and lymphatic tissue was dissected between the nerves. Patients with clinical stage I and IIA disease that was lymph node positive at laparoscopic retroperitoneal lymph node dissection did not receive additional chemotherapy. RESULTS: Surgery was successfully completed in all patients and no conversion to open surgery was necessary. Mean operative time was 323 minutes. No intraoperative complications occurred. Of patients with stage I and marker negative stage IIA disease active tumor was found in 5 retroperitoneal lymph node dissection specimens, and no patients had recurrence. Of 19 patients with post-chemotherapy stage IIB disease teratoma was found in the lymphatic tissue in 4 (21.0%). No retroperitoneal recurrence was observed. Pulmonary metastases developed 9 months after surgery in 1 patient with stage I disease and negative retroperitoneal histology, and were treated successfully. All patients are currently free of disease at a mean followup of 17.2 months. Antegrade ejaculation was preserved in 36 patients (85.7%). CONCLUSIONS: Bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection is feasible and associated with low morbidity if performed by experienced hands. The oncological efficacy of this approach is promising and currently under evaluation.

Extended focal radiotherapy of 30 Gy alone for intracranial synchronous bifocal germinoma: a single institute experience.

OBJECTS: To evaluate the disease characteristics and treatment outcomes for patients with intracranial synchronous bifocal germinomas treated with extended focal irradiation alone. METHODS: Between January 1996 and March 2007, seven patients (three males and four females) with intracranial synchronous bifocal germinomas treated at Taipei Veterans General Hospital were reviewed. The median age at diagnosis was 14 years (range, 11-28 years). Four patients had surgery before radiotherapy. All patients underwent extended focal irradiation encompassing the whole ventricle system with a total radiation dose of 30 Gy (2 Gy daily). No patient received scheduled systemic chemotherapy before or after radiotherapy. Disease characteristics, treatment outcomes, and the impact of lesion numbers (single vs. bifocal) on survivals were investigated. RESULTS: With a median follow-up time of 49 months (range, 20-66 months), the 2- and 5-year survival rates were both 100%. After treatment, all patients had good performance without recurrence. No severe complication was observed. In comparison, the overall survival (OS, p = 0.475) and the disease-free survival (DFS, p = 0.537) rates were not significantly different between bifocal- and single-lesion groups. Lesion numbers did not affect both OS and DFS. In addition, the incidence of neuraxial seeding was not higher in patients with bifocal germinomas as compared to those with single lesion. CONCLUSIONS: Intracranial germinomas are extremely radiosensitive. Young patients with synchronous bifocal germinomas could be successfully treated with extended focal 30-Gy radiotherapy alone. The therapeutic advantage using this regimen needs to be further evaluated with larger sample size and longer follow-up time.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the "good prognosis" group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the "intermediate and poor prognosis" group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24­30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28­261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.

High-dose chemotherapy with autologous hematopoietic stem cell support for solid tumors in adults.

Supported by experimental evidence and convincing results of early phase II studies, since the 1980s high-dose chemotherapy (HDC) with autologous hematopoietic stem cell support (AHSCT) has been uncritically adopted by many oncologists as a potentially curative option for several solid tumors. As a result, the number (and size) of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) in this setting was limited and the benefit of a greater escalation of dose of chemotherapy with stem cell transplantation in solid tumors remains, with the possible exception of breast carcinoma (BC) and germ cell tumors (GCT), largely unsettled. In this article, we review and comment on the data from studies to date of HDC for solid tumors in adults.